Objectives: To investigate the cytotoxicity of TRA-8, an antibody that specifically binds death receptor 5 (DR5), alone and in combination with cisplatin, using an ex vivo human cervical cancer model.
Methods: Fifteen cervical cancer specimens were obtained at the time of radical hysterectomy and tumor slices were prepared with the Krumdieck tissue slicer. Tumor slices were exposed to varying concentrations of TRA-8, cisplatin, or the combination of TRA-8 and cisplatin. Using non-linear modeling, dose response curves and IC50 values were generated for each specimen treated with TRA-8. The additive cytotoxic effect of combination treatment was evaluated as well. In addition to ATP viability assays, treated and untreated slices were assessed by immunohistochemistry (IHC) and western blot analysis to confirm apoptosis induction via the extrinsic pathway.
Results: Eleven patient specimens yielded TRA-8-induced IC50 values. Sixty-four percent were found to be sensitive to TRA-8-induced cytotoxicity at IC50 doses less than 1000 ng/ml. Seven patient specimens underwent combination treatment with TRA-8 and cisplatin. Of these specimens, 86% exhibited additive cytotoxicity in comparison to treatment with either agent alone. IHC revealed an increase in DR5 expression in tumor slices treated with cisplatin for 24 h. IHC and Western blotting demonstrated TRA-8-induced cell death via apoptosis and activation of caspase 3 and 8.
Conclusions: This study confirms the utility of an ex vivo human cervical cancer model, to evaluate the anti-tumor activity of TRA-8 and cisplatin. This model may be a useful pre-clinical tool to assess cytotoxicity and mechanistic properties of novel agents in cervical cancer.
Curzerenone is a major component of the traditional herbal medicine Curcumae Rhizoma with potential cancer-suppressing effects. This study aims to investigate the treatment effect of Curzerenone on cervical cancer cells and the underpinning mechanism. HeLa and SiHa cells were treated with Curzerenone.
Patients with esophageal cancer and concomitant liver cirrhosis (LC) pose a surgical challenge because of the increased risk of postoperative complications and mortality. Purpose of this study was to review the existing literature and estimate perioperative short-term outcomes of esophagectomy in this patient population. Systematic review and meta-analysis.
Cervical lymph node metastasis (LNM) is an important prognostic factor for hypopharynx squamous cell carcinoma (SCC) patients, which can be detected in a large fraction of clinically diagnosed early hypopharynx SCC patients; however, the importance of knowing the risk of LNM in the younger/older patients has not been well defined. The objective of this study is to assess the effect of age and LNM in T1-2 hypopharynx SCC patients. Patients with T1-2 hypopharynx SCC were extracted from the Surveillance, Epidemiology and End Results database between 2005 and 2014.
Virological Diagnostic Laboratory, Department of Microbiology and Parasitology, Biomedical Institute, Universidade Federal Fluminense, Niteroi, Brazil.
Background: Human papillomavirus (HPV) infection profoundly affects women living with HIV (WLWH). This infection leads to cervical cancer (CC) and increased mortality.
Methods: This study monitored HPV infection in WLWH in Rio de Janeiro, Brazil, before (T1) and after (T2) 4 years of vaccination.
